Adult sheep have either high potassium (HK) or low potassium (LK) red cells with kinetically and quantitatively different Na ion K ion pumps and qualitatively distinct Na ion K ion leaks. This genetic HK/LK dimorphism is also associated with the M and L membrane antigens, the L substance acting as an inhibitor of the Na ion K ion pump in LK red cells. After massive hemorrhage, adult LK sheep temporarily produce HK type red cells, which apparently assume gradually LK character. With the advent of new technology (electric sizing) and advance in the field of cation transport, it is proposed to investigate the membrane molecular changes in cation transport and M/L antigens during maturation of reticulocytes into mature red cells, in both HK and LK sheep. Especially, the more than 10 fold changes in Na ion K ion pump flux preliminarily observed by us to occur within a few days in the newly appearing reticulocyte population of anemic LM sheep will be analyzed by the means of K ion flux measurements and 3H-ouabain binding in order to define whether there occur molecular turnover changes and/or diminuition of Na ion k ion pump sites, and how these changes correlate with the gradual appearance of the L antigen. The 5-10 fold enhanced ouabain insensitive K ion leak flux recently found by us will be studied, especially in the light of our new finding that the LK gene may control a chloride dependent K ion transport system which can be activated by N-ethylmaleimide (NEM) only in LK sheep and LK goat red cells, without altering the Na ion permeability. Hence kinetic characterization of the NEM-induced K ion/Cl minus transport in mature LK cells will be studied prior to the proposed detailed analysis of the passive K ion transport changes in maturing HK and LK reticulocytes. Further studies on the biochemical nature of the M and L antigens are proposed to exploit more recent techniques of membrane labelling, affinity chromatography, and affinity directed cross linking of anti-M/L to their respective antigenetic sites. The long term objectives are an increased understanding of the molecular basis of the HK/LK transition in sheep erythrocytes, in particular, and of differentiation and/or aging of ion transport processes in biological membranes, in general.